AFM13 in Patients with Relapsed or Refractory Hodgkin Lymphoma: Final Results of an Open-Label, Randomized, Multicenter Phase II Trial

The outcome of patients (pts) with classical Hodgkin Lymphoma (cHL) experiencing relapse after high dose chemotherapy, brentuximab vedotin (BV) and anti-PD1 antibody (Ab) treatment is poor and in most patients the duration of the response to this treatment is rather short. Thus, there still is a need for new treatment options. A promising immunotherapeutic approach is the bispecific anti-CD30/CD16A antibody AFM13. Pts ≥ 18 years with relapsed or refractory cHL after standard therapy including BV and anti-PD1 Ab were included in this two-stage trial (NCT02321592). In stage I pts were initially assigned in a 1:1 ratio to either Arm A with 1.5 mg/kg AFM13 3x/ week for 8 weeks or Arm B with 1.5 mg/kg AFM13 3x/ week for 2 weeks followed by 1 infusion of 7.0 mg/kg/week for 6 weeks. After an amendment to this trial, all further pts received 7 mg/kg per week, with 1 mg/kg loading dose and 6 mg/kg as continuous infusion for 5 days/ week thereafter (Arm C). If ≥ 2 overall responders were observed in 10 pts, the respective trial arm qualified for stage 2. Primary endpoint was the objective response (complete/partial remission (CR/PR)) after the first cycle. Secondary endpoints included efficacy (Overall survival (OS), Progression free survival (PFS)) and safety analyses. Between June 26, 2015 and May 31, 2019, 25 pts were assigned to arm A (n=5), B (n=12), or C (n=8), respectively, and qualified for statistical analyses. Median age of the study population was 45 (range 21-73) years. 24/25 patients were male. Clinical stages 2, 3 and 4 were diagnosed in 8 (32%), 9 (36%), and 8 (32%) patients, respectively. Patients had received a median of 3 (range 1-11) salvage-therapy lines after first-line therapy. Since the trial was terminated in stage I due to a lack of recruitment, all statistical analyses of primary and secondary endpoints are also of descriptive nature. The central response evaluation panel included 24 of 25 pts: The objective response rate was 16.6% including 1 complete response (CR) and 3 partial responses (PR). Stable disease (SD) was documented in 6 pts and progressive disease (PD) in 14 pts. The responses were distributed as follows to the treatment arms: Two responses were documented in arm C and one response was documented in arm A and B, respectively. Second cycle AFM13 was started in 5 patients. Two patients had PD during or after cycle 2, and one patient each was diagnosed with CR, PR, or SD. During follow-up, there were 22 cases of PD and 9 deaths.